Four investigators from one clinical and two basic science departments will explore aspects of autoantibody formation and regulation in autoimmune disease and of cell mediated immunity. The first two projects focus on anti-DNA antibodies in systemic lupus, the structural basis for antigen binding and pathogenicity and the regulation of expression DNA binding antibodies. The third project is an exploits an idiotypic approach to understand the molecular genetics of rheumatoid factors in rheumatoid arthritis. The fourth project exploits a novel methodology for studying self peptides associated with MHC antigens to identify tissue specific self peptides. The investigators will share 3 core facilities funded by this grant, an administrative core, an oligonucleotide synthesis core, and an animal core, as well as additional core facilities supported by other sources. The investigators in this program are highly interactive. This application reflects the continuing commitment of some of the investigators to the study of human disease and the new focus of others on issues relevant to human pathobiology.